Value of multi-modality small fiber assessments in a genotypically diverse cohort of transthyretin-related amyloidosis in the early stages of disease
Bibliographic record
Abstract
Transthyretin-related amyloidosis (ATTRv) is a progressive multisystem disorder, predominantly involving the peripheral nerve system (PNS) and heart. Quantification of small fiber damage may help guide treatment decisions, as amyloid deposits frequently affect those fibers early in disease course. Corneal confocal microscopy (CCM) is a promising method to monitor patients with ATTRv, due to similarities between corneal nerves and PNS, as the cornea is innervated by Aδ and C fibers. We compared CCM measures from ATTRv patients to a group of healthy individuals, matched by age and gender. We then investigated the correlations between small fiber tests (SFT): CCM, LDI-Flare and CDT, COMPASS-31 and disability scales (RODS and ONLS) in patients. Of 20 patients (6 with V30M), mean age 50.3 ± 15.3Y, 7 female (35%), six (30%) had polyneuropathy and 10 (50%) carpal tunnel syndrome. CDT was abnormal in 9 and LDI-flare in 6 patients. CCM was abnormal in 19 tested patients and significantly reduced when compared to controls (CNFL: 6.31 ± 0.31 vs. 15.21 ± 1.02 mm/mm 2 , p < 0.001). Mean COMPASS-31-scores were 22.27 ± 22.84; RODS and ONLS were 38.15 ± 12.33 and 2.05 ± 2.3, with no significant differences between sub-group scores. Disease duration was significantly correlated with ONLS (0.43, p = 0.05) and RODS (0.46, p = 0.03). There were no significant correlations between measures of disability and SFT. In a diverse cohort of ATTRv patients, CCM was the most frequent abnormal measurement. CCM can be a useful test to triage patients in the early disease stages and with few or equivocal symptoms. La amiloidosis por transtiretina (ATTRv) es un trastorno multisistémico progresivo que afecta predominantemente el sistema nervioso periférico (SNP) y el corazón. La cuantificación del daño de las fibras pequeñas puede guiar las decisiones de tratamiento, ya que los depósitos de amiloide frecuentemente afectan esas fibras en el comienzo de la enfermedad. La microscopia confocal corneal (MCC) es un método prometedor para monitorear la ATTRv, debido a las similitudes entre la estructura del nervio corneal y el SNP, ya que la córnea está inervada por fibras Aδ y C. Comparamos medidas de MCC de pacientes con ATTRv con un grupo de individuos sanos, emparejados por edad y sexo. Luego investigamos las correlaciones entre pruebas de fibras pequeñas (PFP): MCC, laser Doppler imager flare (LDI- flare ) y cold detection threshold (CDT), así como Composite Autonomic Symptom Score-31 (COMPASS-31) y escalas de discapacidad (RODS y ONLS) en pacientes. De 20 pacientes (seis con V30M) con una edad media de 50,3 ± 15,3 años, y de los cuales siete eran mujeres (35%), seis (30%) tenían polineuropatía y 10 (50%) síndrome del túnel carpiano. La CDT fue anormal en nueve y la LDI- flare en seis pacientes. La MCC fue anormal en los 19 pacientes evaluados y se redujo significativamente en comparación con los controles (longitud de la fibra nerviosa corneal [CNFL]: 6,31 ± 0,31 vs. 15,21 ± 1,02 mm/mm 2 , p < 0,001). Las puntuaciones medias de COMPASS-31 fueron 22,27 ± 22,84. Las escalas RODS y ONLS fueron 38,15 ± 12,33 y 2,05 ± 2,3, sin diferencias significativas entre V30M y no-V30M. La duración de la enfermedad se correlacionó significativamente, ONLS (0,43; p = 0,05) y RODS (-0,46, p = 0,03). No hubo correlaciones significativas entre las medidas de discapacidad y las PFP. En una cohorte diversa de pacientes con ATTRv, las medidas de MCC fueron las anormalidades más frecuentes. La MCC puede ser una prueba útil para clasificar a los pacientes en las primeras etapas de la enfermedad y con síntomas pocos o equívocos.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".